A Cross-project Defect Prediction Model Using Feature Transfer and Ensemble Learning

Cross-project defect prediction (CPDP) trains the prediction models with existing data from other projects (the source projects) and uses the trained model to predict the target projects. To solve two major problems in CPDP, namely, variability in data distribution and class imbalance, in this paper we raise a CPDP model combining feature transfer and ensemble learning, with two stages of feature transfer and the classification. The feature transfer method is based on Pearson correlation coefficient, which reduces the dimension of feature space and the difference of feature distribution between items. The class imbalance is solved by SMOTE and Voting on both algorithm and data levels. The experimental results on 20 source-target projects show that our method can yield significant improvement on CPDP

GWAS Identifies Novel Susceptibility Loci on 6p21.32 and 21q21.3 for Hepatocellular Carcinoma in Chronic Hepatitis B Virus Carriers

Genome-wide association studies (GWAS) have recently identified KIF1B as susceptibility locus for hepatitis B virus (HBV)–related hepatocellular carcinoma (HCC). To further identify novel susceptibility loci associated with HBV–related HCC and replicate the previously reported association, we performed a large three-stage GWAS in the Han Chinese population. 523,663 autosomal SNPs in 1,538 HBV–positive HCC patients and 1,465 chronic HBV carriers were genotyped for the discovery stage. Top candidate SNPs were genotyped in the initial validation samples of 2,112 HBV–positive HCC cases and 2,208 HBV carriers and then in the second validation samples of 1,021 cases and 1,491 HBV carriers. We discovered two novel associations at rs9272105 (HLA-DQA1/DRB1) on 6p21.32 (OR = 1.30, P = 1.13×$10^{−19}$) and rs455804 (GRIK1) on 21q21.3 (OR = 0.84, P = 1.86×$10^{−8}$), which were further replicated in the fourth independent sample of 1,298 cases and 1,026 controls (rs9272105: OR = 1.25, P = 1.71×$10^{−4}$; rs455804: OR = 0.84, P = 6.92×$10^{−3}$). We also revealed the associations of HLA-DRB1*0405 and 0901*0602, which could partially account for the association at rs9272105. The association at rs455804 implicates GRIK1 as a novel susceptibility gene for HBV–related HCC, suggesting the involvement of glutamate signaling in the development of HBV–related HCC

Magnetoelectric interaction and transport behaviours in magnetic nanocomposite thermoelectric materials

How to suppress the performance deterioration of thermoelectric materials in the intrinsic excitation region remains a key challenge. The magnetic transition of permanent magnet nanoparticles from ferromagnetism to paramagnetism provides an effective approach to finding the solution to this challenge. Here, we have designed and prepared magnetic nanocomposite thermoelectric materials consisting of BaFe12O19 nanoparticles and Ba0.3In0.3Co4Sb12 matrix. It was found that the electrical transport behaviours of the nanocomposites are controlled by the magnetic transition of BaFe12O19 nanoparticles from ferromagnetism to paramagnetism. BaFe12O19 nanoparticles trap electrons below the Curie temperature (TC) and release the trapped electrons above the TC, playing an ‘electron repository’ role in maintaining high figure of merit ZT. BaFe12O19 nanoparticles produce two types of magnetoelectric effect—electron spiral motion and magnon-drag thermopower—as well as enhancing phonon scattering. Our work demonstrates that the performance deterioration of thermoelectric materials in the intrinsic excitation region can be suppressed through the magnetic transition of permanent magnet nanoparticles

miR‐155 promotes macrophage pyroptosis induced by Porphyromonas gingivalis through regulating the NLRP3 inflammasome

ObjectiveThe aim of this study is to detect pyroptosis in macrophages stimulated with Porphyromonas gingivalis and elucidate the mechanism by which P. gingivalis induces pyroptosis in macrophages.MethodsThe immortalized human monocyte cell line U937 was stimulated with P. gingivalis W83. Flow cytometry was carried out to detect pyroptosis in macrophages. The expression of miR‐155 was detected by real‐time PCR and inhibited using RNAi. Suppressor of cytokine signaling (SOCS) 1, cleaved GSDMD, caspase (CAS)‐1, caspase‐11, apoptosis‐associated speck‐like protein (ASC), and NOD‐like receptor protein 3 (NLRP3) were detected by Western blotting, and IL‐1β and IL‐18 were detected by ELISA.ResultsThe rate of pyroptosis in macrophages and the expression of miR‐155 increased upon stimulation with P. gingivalis and pyroptosis rate decreased when miR‐155 was silenced. GSDMD‐NT, CAS‐11, CAS‐1, ASC, NLRP3, IL‐1β, and IL‐18 levels increased, but SOCS1 decreased in U937 cells after stimulated with P. gingivalis. These changes were weakened in P. gingivalis‐stimulated U937 macrophages transfected with lentiviruses carrying miR‐155 shRNA compared to those transfected with non‐targeting control sequence. However, there was no significant difference in ASC expression between P. gingivalis‐stimulated shCont and shMiR‐155 cells.ConclusionsPorphyromonas gingivalis promotes pyroptosis in macrophages during early infection. miR‐155 is involved in this process through regulating the NLRP3 inflammasome.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152887/1/odi13198_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152887/2/odi13198.pd

Nanoscale integrin cluster dynamics controls cellular mechanosensing via FAKY397 phosphorylation

Transduction of extracellular matrix mechanics affects cell migration, proliferation, and differentiation. While this mechanotransduction is known to depend on the regulation of focal adhesion kinase phosphorylation on Y397 (FAKpY397), the mechanism remains elusive. To address this, we developed a mathematical model to test the hypothesis that FAKpY397-based mechanosensing arises from the dynamics of nanoscale integrin clustering, stiffness-dependent disassembly of integrin clusters, and FAKY397 phosphorylation within integrin clusters. Modeling results predicted that integrin clustering dynamics governs how cells convert substrate stiffness to FAKpY397, and hence governs how different cell types transduce mechanical signals. Existing experiments on MDCK cells and HT1080 cells, as well as our new experiments on 3T3 fibroblasts, confirmed our predictions and supported our model. Our results suggest a new pathway by which integrin clusters enable cells to calibrate responses to their mechanical microenvironment

Neurocardiology: Cardiovascular Changes and Specific Brain Region Infarcts

There are complex and dynamic reflex control networks between the heart and the brain, including cardiac and intrathoracic ganglia, spinal cord, brainstem, and central nucleus. Recent literature based on animal model and clinical trials indicates a close link between cardiac function and nervous systems. It is noteworthy that the autonomic nervous-based therapeutics has shown great potential in the management of atrial fibrillation, ventricular arrhythmia, and myocardial remodeling. However, the potential mechanisms of postoperative brain injury and cardiovascular changes, particularly heart rate variability and the presence of arrhythmias, are not understood. In this chapter, we will describe mechanisms of brain damage undergoing cardiac surgery and focus on the interaction between cardiovascular changes and damage to specific brain regions.</jats:p

Effect of HHFNC therapy on organ oxygenation and brain metabolism in neonates receiving exchange transfusion

BackgroundExchange transfusion therapy is a complex and invasive procedure with a high risk coefficient. This method involves replacing the entire blood of a child with fresh blood with double circulating blood volume in a short period, typically in 1–2 h. This procedure can cause the body's internal environment to be unstable, which can put newborns under a lot of stress. This stress can lead to many, including abnormal laboratory biochemical examination, low or high blood pressure, and apnea. There is also the possibility of secondary infection and, in severe cases, cardiac arrest. This study investigated the effects of Humidified high-flow nasal cannula (HHFNC) ventilation on hemodynamic stability and oxygenation during exchange transfusion in neonates. Furthermore, the effects on brain metabolism and salivary cortisol during exchange transfusion were also analyzed.MethodsIn this study, the control group consisted of 45 cases of children who underwent simple blood exchange between 1 May 2017, and 31 December 2019 control group. The observation group consisted of 33 cases of children who underwent blood exchange under HHFNC support between 1 January 2020, and 30 April 2022. The study compared various physiological parameters between the control and the observation group. These included blood gas analysis, pulmonary artery pressure, ejection fraction, invasive mean arterial pressure, heart rate, cerebral oxygenation, intestinal oxygenation, renal oxygenation, and duration of blood exchange. Furthermore, the study also compared the changes in brain metabolic and salivary cortisol indicators between the two groups of children.ResultsThe results did not reveal any significant difference in PH, PaO2, and duration of blood exchange between the control and the observation group. However, the observation group's invasive mean arterial pressure, ejection fraction, cerebral oxygenation, intestinal oxygenation, and renal oxygenation were higher than those of the control group. Furthermore, compared with the control group, the pulmonary artery pressure, heart rate, and PaCO2 were lower in the observation group. There was a statistically significant difference between the two groups of children in the relevant clinical indicators (total bilirubin, hemoglobin, SPO2, etc.) after exchange transfusion. After 1 h of blood exchange and after blood exchange, the salivary cortisol levels of the observation group were lower than the control group. The difference was statistically significant. The NAA/Cho and Cho/Cr values of the two groups of children were also significantly different.ConclusionDuring blood exchange, unstable hemodynamics substantially impact organ oxygenation. The results of this study suggest that HHFNC and specific ventilation pressure support can improve the respiratory rate and help maintain blood flow stability and organ oxygenation. This technique can also reduce adverse reactions caused by blood exchange, minimizing patient stress and reducing the impact on brain metabolism

Enhanced anti−tumor efficacy of “IL−15 and CCL19” −secreting CAR−T cells in human glioblastoma orthotopic xenograft model

Despite the remarkable success of CAR-T cell therapy in hematologic malignancies, its progress in solid tumors has been slow. Overcoming challenges such as the recruitment and infiltration of CAR-T cells into the tumor site and the survival issues in the harsh tumor microenvironment are crucial for successful application in solid tumors. In this study, CAR-T cells were engineered to secrete both IL-15 and CCL19, and their efficacy was evaluated in a human glioblastoma orthotopic xenograft model. The results reveal that 15 × 19 CAR-T cells exhibit superior proliferation, chemotaxis, and phenotypic characteristics compared to conventional CAR-T cells in vitro. In vivo, 15 × 19 CAR-T cells exhibit superior control over tumors compared to conventional counterparts. Mechanistically, the improved efficacy can be attributed, in part, to IL-15 and CCL19 enhancing T-cell infiltration at the tumor site and fortifying resistance to exhaustion within the tumor microenvironment. In conclusion, the incorporation of IL-15 and CCL19 into CAR-T cells emerges as a promising strategy to elevate the anti-tumor efficacy of CAR-T cell therapy, positioning 15 × 19 CAR-T cells as a potential breakthrough for enhancing the application of CAR-T therapy in solid tumors

Metabolic and transcriptomic responses of Taxus mairei to nano-pollutants: insights into AgNPs and PsNPs impact

There is a growing global concern regarding the pervasive issue of nano-pollutants. Typical nano-materials, such as polystyrene nanoplastics (PsNPs) and silver nanoparticles (AgNPs), pose significant risks to ecosystems and human health. Taxus mairei is a well-known gymnosperm widely planted in South China and has great medicinal qualities. However, the effects of nano pollutants on the primary and secondary metabolism of Taxus plants have not been sufficiently explored. We investigated the responses of T. mairei to different nano-pollutants via physiological, transcriptomic, and metabolomic analyses. AgNPs and PsNPs significantly affected several secondary and energy metabolism-related pathways, respectively. In T. mairei, AgNPs greatly impacted flavonoid metabolism by regulating the expression of the CHI gene, while PsNPs significantly impacted energy metabolism by regulating the expression of FRK genes. Furthermore, a transcriptional regulation network, including GATA (ctg10916_gene.2), bHLH (ctg495_gene.7), MYB (ctg18368_gene.1), and NAC (ctg8193_gene.1), was predicted to be associated with the responses of T. mairei to nano-pollutants. The present study elucidated a regulatory mechanism underlying the responses of T. mairei to nano-pollutants, which has the potential to aid in the breeding of Taxus species with high environmental adaptability

Charge density wave without long-range structural modulation in canted antiferromagnetic kagome FeGe

Strongly correlated electron systems with a kagome lattice can host abundant exotic quantum states such as superconductivity and spin/charge density waves (CDW) due to the complicated interactions between different degrees of freedoms in the framework of a unique two-dimensional geometrically frustrated lattice structure. Recently, successive orders of A-type antiferromagnetism (AFM), $2\times2\times2$ CDW and canted double-cone AFM have been manifested upon cooling in magnetic kagome FeGe. However, the mechanism of the CDW order and its interaction with magnetism are presently enigmatic at best. Here we investigate the evolution of CDW order with temperature across the spin canting transition in FeGe by single-crystal x-ray diffraction. Refinements of its modulated structure are presented using the superspace approach. Interestingly, the superlattice reflections originating from CDW-induced long-range structural modulation become extremely weak after the system enters the canted AFM while a $2\times2$ CDW in the $ab$ plane persists as a long-range order demonstrated by strong electronic modulation in the d$I$/d$V$ map of scanning tunneling spectroscopy. We discovered a novel CDW order without long-range structural modulation in FeGe probably because of the competition between CDW and canted AFM in determining the underlying crystal structure. In addition, occupational modulations of Ge1 atoms located in the kagome plane and displacive modulations of all the atoms were extracted from the refinements, confirming the existence of Ge atom dimerization along the $c$ axis as the major distortion and indicating a dynamic transformation between different CDW domains.Comment: 22 pages, 6 figures. Comments on the manuscript are welcom